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Information on EC 4.2.2.8 - heparin-sulfate lyase
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EC Tree
4.2.2.8 heparin-sulfate lyaseIUBMB Comments
Does not act on N,O-desulfated glucosamine or N-acetyl-O-sulfated glucosamine linkages.
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Word Map
- 4.2.2.8
- proteoglycans
- glycosaminoglycans
- chondroitinase
- chondroitin
- endothelial
- oligosaccharide
-
basement
- dermatan
-
heparin-binding
-
hspgs
- bfgf
- disaccharide
- hyaluronidase
- heparinum
-
hyaluronic
-
nitrous
- perlecan
- flavobacterium
- chlorate
- neuraminidase
-
3hglucosamine
- fgf-2
- antithrombin
-
n-sulfated
-
iduronic
- lyases
-
glycocalyx
-
35ssulfate
- keratanase
-
heparin-like
-
proteoheparan
-
inner-core
- analysis
-
heptose
-
cetylpyridinium
-
beta-d-xyloside
-
trifluoromethanesulfonic
- synthesis
-
sulfate-containing
- heparanase
-
glycosaminoglycan-degrading
-
densa
-
35so4-labeled
- hno2
-
cuprolinic
-
6-o-sulfate
-
sulfate-binding
- glypican-1
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
Synonyms
heparitinase, heparinase iii, heparitinase i, hep i, hepiii, heparin lyase iii, heparan sulfate lyase, heparitin-sulfate lyase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
BT4657
Hep III
heparan sulfate lyase
-
-
-
-
heparin lyase III
-
-
-
-
heparin sulfate eliminase
-
-
-
-
heparin-sulfate eliminase
-
-
-
-
heparinase III
heparitin sulfate lyase
-
-
-
-
heparitin-sulfate lyase
-
-
-
-
heparitinase
heparitinase I
heparitinase II
-
-
-
-
HepIII
lyase, heparin sulfate
-
-
-
-
heparitinase I
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
[GlcAbeta(1-4)GlcNbeta(1-4)]n = [GlcAbeta(1-4)GlcNbeta(1-4)]n-1 + 2-amino-2-deoxy-4-O-alpha-L-threo-hex-4-enopyranuronosyl-beta-D-glucopyranose
[GlcAbeta(1-4)GlcNbeta(1-4)]n = [GlcAbeta(1-4)GlcNbeta(1-4)]n-1 + 2-amino-2-deoxy-4-O-alpha-L-threo-hex-4-enopyranuronosyl-beta-D-glucopyranose
-
-
-
-
[GlcAbeta(1-4)GlcNbeta(1-4)]n = [GlcAbeta(1-4)GlcNbeta(1-4)]n-1 + 2-amino-2-deoxy-4-O-alpha-L-threo-hex-4-enopyranuronosyl-beta-D-glucopyranose
His295 and His510 are essential for catalytic activity
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
-
-
-
-
elimination of sulfate
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
-
-
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SYSTEMATIC NAME
IUBMB Comments
heparin-sulfate lyase
Does not act on N,O-desulfated glucosamine or N-acetyl-O-sulfated glucosamine linkages.
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CAS REGISTRY NUMBER
COMMENTARY
37290-86-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcN-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4)-alpha-D-GlcN
-
-
-
?
4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcNAc-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4)-alpha-D-GlcNAc
4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcNAc6S-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4)-alpha-D-GlcNAc6S
-
-
-
?
4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcNS-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4)-alpha-D-GlcNS
-
-
-
?
4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcNS6S-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4)-alpha-D-GlcNS6S
-
-
-
?
4-nitrophenyl beta-D-GlcA-(1->4>)-alpha-D-GlcNS-(1->4)-beta-IdoA2S-(1->4)-alpha-D-GlcNS-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4>)-alpha-D-GlcNS-(1->4)-beta-IdoA2S-(1->4)-alpha-D-GlcNS
-
-
-
?
beta-D-glucopyranosyluronic acid
?
-
major requirement for enzyme action is reduced sulfation, cannot cleave linkages containing unsulfated GalAP residues
-
-
?
heparan sulfate
non-sulfated di- and tetrasaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends + SO42-
hyaluronate
unsaturated hyaluronate disaccharide
-
no substrate of wild-type, but substrate of mutant K130C. Reaction of EC 4.2.2.1
-
-
?
N,6-sulfated glucosaminido-alpha-1,4-glucuronic acid oligosaccharide
N-sulfated glucosaminido-alpha-1,4-glucuronic acid oligosaccharide + 6-sulfated glucosaminido-alpha-1,4-glucuronic acid oligosaccharide + SO42-
-
heparitinase II
heparitinase II
?
N-acetylated heparan-sulfate
N-acetylated disaccharides
-
heparitinase I
hepartitinase I
?
N-acetylated heparan-sulfate
N-sulfated disaccharides
-
heparitinase I
hepartitinase I
?
partially de-N-acetylated polysaccharide of Escherichia coli K5 strain
(DELTA4,5-unsaturated hexuronic acid)-(N-unsubstituted glucosamine)-(hexuronic acid)-(N-acetylglucosamine)
-
the polysaccharide consists of the repeating linear sequence -4GlcAbeta1-4GlcNAcalpha1-. Under controlled conditions for partial digestion, lyase III does not act at the GlcN-GlcA linkage, whereas GlcNAc-GlcA is cleaved. Under forced conditions for exhaustive digestion, the GlcN-GlcA linkage is only partially cleaved
-
-
?
partially de-N-sulfated forms of heparin
(DELTA4,5-unsaturated hexuronic acid)-(N-unsubstituted glucosamine)
-
heparinase III
-
-
?
unsulfated alpha-L-idopyranosyluronic acid
?
-
major requirement for enzyme action is reduced sulfation, cannot cleave linkages containing unsulfated GalAP residues
-
-
?
4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcNAc-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4)-alpha-D-GlcNAc
-
-
-
?
4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcNAc-(1->4)-beta-D-GlcA
4-nitrophenyl 4-deoxy-alpha-L-threo-hex-4-enopyranosiduronic acid + beta-D-GlcA-(1->4)-alpha-D-GlcNAc
about 15fold higher catalytic efficiency than with 4-nitrophenyl beta-D-GlcA-(1->4)-alpha-D-GlcNS-(1->4)-beta-D-GlcA
-
-
?
desulfated N-sulfated heparosan
desulfated N-sulfated heparosan disaccharide
-
-
-
?
desulfated N-sulfated heparosan
desulfated N-sulfated heparosan disaccharide
-
-
-
?
heparan sulfate
n alpha-deltaUA-glcNAc
-
major product
-
?
heparan sulfate
non-sulfated di- and tetrasaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends + SO42-
-
-
-
?
heparan sulfate
non-sulfated di- and tetrasaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends + SO42-
-
-
-
?
heparan sulfate
non-sulfated di- and tetrasaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends + SO42-
-
-
-
?
heparan sulfate
non-sulfated di- and tetrasaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends + SO42-
-
-
-
?
heparan sulfate
non-sulfated di- and tetrasaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends + SO42-
-
-
-
?
N-desulfated, N-acetylated heparin
N-desulfated, N-acetylated heparin disaccharide
-
-
-
?
N-desulfated, N-acetylated heparin
N-desulfated, N-acetylated heparin disaccharide
-
-
-
?
additional information
?
-
-
cleavage/degradation of heparin forming unsaturated uronic acid
-
-
?
additional information
?
-
-
the enzyme is capable of tolerating heparin sulfate trimers containing single GlcNH2, GlcNAc6S or GlcNS6S residues, but is more than 20 times less reactive towards the secondary cleavage sites compared with the counterpart primary substrates. Hep III hydrolyzes the iduronic acid containing glyosidic linkage (GlcNS-IdoA) at similar catalytic efficiency to GlcNS-GlcA, but has a slight preference toward GlcNS-GlcA linkage over GlcNS-IdoA at the beginning of catalytic reaction
-
-
?
additional information
?
-
the enzyme is capable of tolerating heparin sulfate trimers containing single GlcNH2, GlcNAc6S or GlcNS6S residues, but is more than 20 times less reactive towards the secondary cleavage sites compared with the counterpart primary substrates. Hep III hydrolyzes the iduronic acid containing glyosidic linkage (GlcNS-IdoA) at similar catalytic efficiency to GlcNS-GlcA, but has a slight preference toward GlcNS-GlcA linkage over GlcNS-IdoA at the beginning of catalytic reaction
-
-
?
additional information
?
-
-
the susceptibility of the oligosaccharide substrates to the enzymatic digestion is size-dependent. Hep III has a preference for cleavage of the internal glycosidic linkages over those near to nonreducing/reducing ends . Hep III hydrolyzes the IdoA-containing glyosidic linkage (GlcNS-IdoA) at similar catalytic efficiency to GlcNS-GlcA, but has a slight preference toward GlcNS-GlcA linkage over GlcNS-IdoA at the beginning of catalytic reaction. The IdoA2S residue significantly decreases the reactivity of Hep III towards its adjacent GlcNS-GlcA at reducing end of heparan sulfate oligosaccharides, but shows no obvious influence on its nearby cleavage site at the nonreducing end
-
-
?
additional information
?
-
the susceptibility of the oligosaccharide substrates to the enzymatic digestion is size-dependent. Hep III has a preference for cleavage of the internal glycosidic linkages over those near to nonreducing/reducing ends . Hep III hydrolyzes the IdoA-containing glyosidic linkage (GlcNS-IdoA) at similar catalytic efficiency to GlcNS-GlcA, but has a slight preference toward GlcNS-GlcA linkage over GlcNS-IdoA at the beginning of catalytic reaction. The IdoA2S residue significantly decreases the reactivity of Hep III towards its adjacent GlcNS-GlcA at reducing end of heparan sulfate oligosaccharides, but shows no obvious influence on its nearby cleavage site at the nonreducing end
-
-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
additional information
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
diethyl dicarbonate
-
inactivation, 80% reversible by hydroxylamine within 6 h, mapping of modified histidine residues
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Sialoglycopeptides obtained from a transplantable rat colorectal adenocarcinoma: a comparison with those from normal colonic mucosa.
Albuminuria
Essential role and therapeutic targeting of the glomerular endothelial glycocalyx in lupus nephritis.
Albuminuria
Removal of heparan sulfate from the glomerular basement membrane blocks protein passage.
Arthritis
FGF-2 is bound to perlecan in the pericellular matrix of articular cartilage, where it acts as a chondrocyte mechanotransducer.
Bone Resorption
J774A.1 macrophage cell line produces PDGF-like and non-PDGF-like growth factors for bone cells.
Carcinoma
Ovarian carcinoma cells synthesize both chondroitin sulfate and heparan sulfate cell surface proteoglycans that mediate cell adhesion to interstitial matrix.
Carcinoma
VEGF release by MMP-9 mediated heparan sulphate cleavage induces colorectal cancer angiogenesis.
Carcinoma, Hepatocellular
Degradative removal of heparan sulfate from the surface of an ascites hepatoma, AH 66, by heparitinase.
Corneal Dystrophies, Hereditary
Abnormal product of corneal explants from patients with macular corneal dystrophy.
Dengue
Internalization and propagation of the dengue virus in human hepatoma (HepG2) cells.
Dengue
Productive dengue virus infection of human endothelial cells is directed by heparan sulfate-containing proteoglycan receptors.
Glaucoma
Flicker defined form perimetry in glaucoma suspects with normal achromatic visual fields.
Infections
Cell membrane bound N-acetylneuraminic acid is involved in the infection of fibroblasts and phorbol-ester differentiated monocyte-like cells with human cytomegalovirus (HCMV).
Infections
Cell-surface heparan sulfate facilitates human immunodeficiency virus Type 1 entry into some cell lines but not primary lymphocytes.
Infections
Cell-surface heparan sulfate proteoglycan mediates HIV-1 infection of T-cell lines.
Infections
Cellular invasion of Orientia tsutsugamushi requires initial interaction with cell surface heparan sulfate.
Infections
Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses.
Infections
Membrane-associated heparan sulfate is not required for rAAV-2 infection of human respiratory epithelia.
Infections
Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors.
Infections
Primary attachment of murine leukaemia virus vector mediated by particle-associated heparan sulfate proteoglycan.
Infections
Role of cell surface glycosaminoglycans of human T cells in human immunodeficiency virus type-1 (HIV-1) infection.
Infections
Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus.
Infections
Shielding of a lipooligosaccharide IgM epitope allows evasion of neutrophil-mediated killing of an invasive strain of nontypeable Haemophilus influenzae.
Infections
The initial steps leading to papillomavirus infection occur on the basement membrane prior to cell surface binding.
Measles
Analysis of the molecules involved in human T-cell leukaemia virus type 1 entry by a vesicular stomatitis virus pseudotype bearing its envelope glycoproteins.
Melanoma
A synthetic peptide from the heparin-binding domain III (repeats III4-5) of fibronectin promotes stress-fibre and focal-adhesion formation in melanoma cells.
Melanoma
Cell surface phosphatidylinositol-anchored heparan sulfate proteoglycan initiates mouse melanoma cell adhesion to a fibronectin-derived, heparin-binding synthetic peptide.
Melanoma
Glycosaminoglycans of cultured human fetal uveal melanocytes and comparison with those produced by cultured human melanoma cells.
Neoplasm Metastasis
Decreasing the metastatic potential in cancers--targeting the heparan sulfate proteoglycans.
Neoplasm Metastasis
Partial sequence of human platelet heparitinase and evidence of its ability to polymerize.
Neoplasm Metastasis
Platelet-tumor cell interaction with the subendothelial extracellular matrix: relationship to cancer metastasis.
Neoplasms
Decreasing the metastatic potential in cancers--targeting the heparan sulfate proteoglycans.
Neoplasms
Expression of N-CAM by human renal cell carcinomas correlates with growth rate and adhesive properties.
Neoplasms
Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis.
Neoplasms
Interference with tumor cell-induced degradation of endothelial matrix on the antimetastatic action of nafazatrom.
Neoplasms
Partial characterization of proteoglycans synthesized by human glomerular epithelial cells in culture.
Neoplasms
Partial sequence of human platelet heparitinase and evidence of its ability to polymerize.
Neoplasms
Platelet-tumor cell interaction with the subendothelial extracellular matrix: relationship to cancer metastasis.
Neoplasms
The syndecan-1 heparan sulfate proteoglycan is a viable target for myeloma therapy.
Neuroblastoma
A cell-surface heparan sulfate proteoglycan mediates neural cell adhesion and spreading on a defined sequence from the C-terminal cell and heparin binding domain of fibronectin, FN-C/H II.
Ovarian Neoplasms
[Hypoxia increases the expression of heparitinase and the invasiveness through the hypoxia inducible factor-1alpha dependent pathway in human ovarian cancer cell line SKOV3]
Reperfusion Injury
Heparinase III exerts endothelial and cardioprotective effects in feline myocardial ischemia-reperfusion injury.
Scleroderma, Diffuse
Compositional changes of urinary acidic glycosaminoglycans in progressive systemic sclerosis.
Thrombasthenia
Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor.
Trachoma
Chlamydia trachomatis glycosaminoglycan-dependent and independent attachment to eukaryotic cells.
Virus Diseases
Sulfated Glycosaminoglycans as Viral Decoy Receptors for Human Adenovirus Type 37.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.438
hyaluronate
-
mutant K130C, pH not specified in the publication, temperature not specified in the publication
0.08
heparan sulfate
-
recombinant wild-type enzyme and mutant H225A, pH 7.6, 35°C
0.08
heparan sulfate
-
wild-type, pH not specified in the publication, temperature not specified in the publication
0.093
heparan sulfate
-
mutant K130C, pH not specified in the publication, temperature not specified in the publication
0.326
heparin
-
wild-type, pH not specified in the publication, temperature not specified in the publication
0.344
heparin
-
mutant K130C, pH not specified in the publication, temperature not specified in the publication
additional information
additional information
-
kinetic modeling based on inactivation data, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.3
hyaluronate
-
mutant K130C, pH not specified in the publication, temperature not specified in the publication
56
heparan sulfate
-
mutant K130C, pH not specified in the publication, temperature not specified in the publication
68
heparan sulfate
-
wild-type, pH not specified in the publication, temperature not specified in the publication
1.6
heparin
-
mutant K130C, pH not specified in the publication, temperature not specified in the publication
1.9
heparin
-
wild-type, pH not specified in the publication, temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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